The skin constitutes the most important organ of the body and is recognized as one of the main active components of the immune defence system. Three types of epidermal cells participate in this system: the keratinocytes, the melanocytes and the Langerhans' cells. These cells, which are found only in the skin, play a key role in the immune response and in particular in antigen presentation.
Healthy skin is capable of defending itself from external attacks using the means at its disposal. It is known however that the immune system, and more particularly that of the skin, weakens during chronobiological ageing.
In addition, the skin is subjected to constant attack by the environment and by certain chemical products. In particular, the Langerhans' cells are the preferred target for ultraviolet radiation. These attacks result in an immune defence suppressing effect.
This has in particular as consequence a less good destruction of the “sunburn cells” whose accumulation generates cytokines which are themselves capable of generating free radicals and of adversely affecting the dermis (in particular by promoting the degradation of collagen) and the epidermis (in particular by slowing the renewal of the epithelium). These effects contribute towards an acceleration of skin ageing.
An immunostimulatory effect can in this case reestablish the immune functions and more particularly those of the epidermis by strengthening the natural defences of the skin and thus make it possible in particular to combat or prevent the cutaneous signs of ageing.
Bacterial extracts endowed with immunostimulatory properties are known in the prior art. It is moreover known that the lipopolysaccharides (designated hereinafter LPS) anchored in the outer membrane of these bacteria are partly responsible for these properties.
LPSs are complex chemical molecules having a molecular mass of between 8000 and 54 000 daltons, having a stratified structure in three compartments which, from the outside to the inside of the cell, are:
the O antigen, which is a polymer, specific to a given strain, consisting of 1 to 10 units of which each comprises a succession of 5 to 7 sugars, generally amino sugars,
the core, which is a polysaccharide which is highly conserved from one bacterial genus to another and which is linked to lipid A by a molecule specific to Gram-negative bacteria, KDO (2-keto-3-deoxyoctulosonic acid), and
lipid A which anchors the LPS in the outer membrane of the bacterium.
Lipid A is a dimer of glucosamine carrying, through condensation with its hydroxyl groups situated at the 3- and 3′-positions and with its amino groups situated at the 2- and 2′-positions, more or less unsaturated and hydroxylated fatty acids which may themselves be esterified, on their hydroxyl groups, with other fatty acids. It is these fatty acids which allow anchorage of lipid A in the outer membrane of the cell, which is of a phospholipid nature. In addition, their nature (as C12-C18) and their position on glucosamines determine the biological activity of the lipids A and therefore of the LPS(s).
The search for biologically active LPSs is however hampered by the problem of the endotoxicity of these molecules. Indeed, most LPSs possess a lipid A which, once unanchored from the cell membrane, is capable of binding to the CD14 receptors and of activating them, thus causing in particular a release of TNF which is capable of causing a septic shock.
Research studies have been carried out in order to determine which structural factors could influence the agonist or antagonist character of the CD14 receptors for these LPSs. It has been demonstrated that the LPSs of cylindrical shape and/or whose fatty acids are arranged symmetrically on the glucosamine backbone are rather antagonists of CD14, in contrast to the conically shaped and/or asymmetric LPSs (Schromm et al, Eur. J. Biochem. 267 pp 2008-2013 (2000)).